The present invention relates to novel oral dosage forms that protect the epithelial and mucosal tissues of the mouth and the buccal cavity, the pharynx, the larynx, and the esophagus from erosion, ulceration, or other like irritation suffered by direct contact of these tissues with the active ingredient. The tablet is a modified oval shape and is film coated. This invention further relates to a method of treating or preventing diseases characterized by abnormal calcium and phosphate metabolism using the novel film coated dosage forms described herein.
The oral administration of certain active ingredients sometimes results in patient complaints shortly after dosing; said complaints are usually characterized by the patients as heartburn, esophageal burning, pain and/or difficulty upon swallowing, and/or pain existing behind and/or mid-sternum. It is believed that these complaints originate from esophagitis or esophageal irritation caused by the erosion, ulceration, or other like irritation of the epithelial and mucosal tissues of the upper gastrointestinal tract, generally the mouth through the stomach, most generally the esophagus. It is hypothesized that said irritation results from the active ingredient coming in direct contact with those epithelial and mucosal tissues, resulting in the topical irritation thereof. If the dosage form adheres in the esophagus, the active ingredient slowly dissolves and creates a high drug concentration on the mucosal surface of the esophagus.
Particularly problematic drugs are those which when dissolved have a pH below 2-3, drugs with cytotoxic activity (caustic) and/or the local development of a hyperosmolar solution which causes mucosal desiccation. These actives include but are not limited to emperonium bormide, doxycycline, and other tetracyclines/antibiotics, iron preparations, quinidine, nonsteroidal anti-inflammatory drugs, alprenolol, ascorbic acid, captopril, theophylline, zidovoudine (AZT) and bisphosphonates.
Dosage forms have been developed to delay the release of the active ingredients after passage through the upper gastrointestinal tract and in some cases through the stomach, i.e., enteric coated tablets. But, in certain instances its is undesirable or unnecessary for a medicant to be in a delayed release dosage form. Accordingly, it became desirable to develop novel oral dosage forms which would facilitate rapid esophageal transit, minimize or avoid the release of an active compound in the upper gastrointestinal tract and deliver the active ingredient to the stomach. Said novel oral dosage forms are generally oval shaped tablets, including but are not limited to oval, modified oval and caplet shaped tablets and are film coated to facilitate rapid esophageal transit and release the active in the stomach thereby, providing protection to the tissues of the mouth, pharynx, and esophagus. Most preferred are novel modified oval shape, film coated oral dosage forms that contain a bisphonates such as risedronate or alendronate.
The present invention is directed to a pharmaceutical formulation in an oral generally oval shaped, including but not limited to oval, modified oval and caplet shaped form. The dosage form is film coated and comprised of a safe and effective amount of an active ingredient and pharmaceutically-acceptable excipients. Said dosage forms facilitate rapid esophageal transit time thereby avoiding the release of active ingredient in the buccal cavity, pharynx, and esophagus and protecting the epithelial and mucosal tissues thereof from erosion, ulceration or other like irritation.
Accordingly, the novel dosage forms described herein effect the delivery to the stomach of said human or other mammal of a safe and effective amount of active ingredient, and substantially alleviates esophagitis or esophageal irritation which sometimes accompanies the oral administration of certain active ingredients.
The invention further comprises a method of treating diseases characterized by abnormal calcium and phosphate metabolism comprising administering to a human or other mammal afflicted with such a disease a novel oral dosage form containing a bisphosphonate as described herein.